Mizuno Kota, Sakurai Masatoshi, Kato Jun, Yamaguchi Kentaro, Abe Ryohei, Koda Yuya, Kataoka Keisuke, Mori Takehiko
Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Department of Hematology, Tokyo Medical and Dental University, Tokyo, Japan.
Transpl Infect Dis. 2022 Dec;24(6):e13904. doi: 10.1111/tid.13904. Epub 2022 Jul 28.
Letermovir has been approved as a novel cytomegalovirus (CMV) prophylactic agent after allogeneic hematopoietic stem cell transplantation (HSCT). However, there are still insufficient data to properly evaluate the real-world role of letermovir, and the risk factors for CMV reactivation under letermovir prophylaxis have not been clarified.
We performed a single-institution retrospective analysis of patients under prophylaxis with or without letermovir who underwent allogeneic HSCT between March 2012 and December 2019. In August 2018, letermovir was added to the clinical practice at our institution for the prophylaxis of CMV reactivation in allogeneic HSCT recipients. Patients who underwent HSCT without prophylactic letermovir from March 2012 until September 2018 served as a historical control.
The cumulative incidence of clinically significant CMV infection (CS-CMVi) was significantly lower in the letermovir group than in the historical control group not receiving letermovir (30.2% vs. 71.6%, p < .05, at 100 days). In addition, the cumulative incidence of non-relapse mortality (NRM) at day 500 was significantly lower in the letermovir group (4.7% vs. 19.8%, p < .05). We then performed a risk factor analysis for developing CS-CMVi in the letermovir group. The only significant factor identified by this multivariable analysis was transplantation from a CMV seronegative donor to a seropositive recipient (Hazard ratio = 2.76, 95% confidence interval 1.14-6.68, p < .05).
Our study showed that letermovir prophylaxis significantly reduced the incidence of CS-CMVi and NRM in a real-world setting and that the CMV serostatus of the donor remained as a risk factor for CS-CMVi even under letermovir prophylaxis.
来特莫韦已被批准作为异基因造血干细胞移植（HSCT）后新型的巨细胞病毒（CMV）预防药物。然而，目前仍缺乏足够的数据来正确评估来特莫韦在实际应用中的作用，且来特莫韦预防下CMV再激活的危险因素尚未明确。
我们对2012年3月至2019年12月期间接受异基因HSCT且接受或未接受来特莫韦预防的患者进行了单中心回顾性分析。2018年8月，来特莫韦被纳入我们机构的临床实践，用于预防异基因HSCT受者的CMV再激活。2012年3月至2018年9月期间接受HSCT但未接受来特莫韦预防的患者作为历史对照。
来特莫韦组临床上显著的CMV感染（CS-CMVi）累积发生率显著低于未接受来特莫韦的历史对照组（100天时为30.2%对71.6%，p<0.05）。此外，来特莫韦组在第500天时非复发死亡率（NRM）的累积发生率也显著更低（4.7%对19.8%，p<0.05）。然后我们对来特莫韦组发生CS-CMVi的危险因素进行了分析。该多变量分析确定的唯一显著因素是从CMV血清阴性供体移植到血清阳性受体（风险比=2.76，95%置信区间1.14-6.68，p<0.05）。
我们的研究表明，在实际应用中来特莫韦预防可显著降低CS-CMVi和NRM的发生率，并且即使在来特莫韦预防下，供体的CMV血清状态仍是CS-CMVi的一个危险因素。
